chr14-68295488-G-T

Variant names:

• chr14-68295488-G-T
• rs11158728
• NM_133510.4:c.853+3508G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133510.4(RAD51B):​c.853+3508G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 152,000 control chromosomes in the GnomAD database, including 22,972 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (22972 hom., cov: 32)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.342
• Publications: 12 publications found

Genes affected

RAD51B (HGNC:9822): (RAD51 paralog B) The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are evolutionarily conserved proteins essential for DNA repair by homologous recombination. This protein has been shown to form a stable heterodimer with the family member RAD51C, which further interacts with the other family members, such as RAD51, XRCC2, and XRCC3. Overexpression of this gene was found to cause cell cycle G1 delay and cell apoptosis, which suggested a role of this protein in sensing DNA damage. Rearrangements between this locus and high mobility group AT-hook 2 (HMGA2, GeneID 8091) have been observed in uterine leiomyomata. [provided by RefSeq, Mar 2016]

RAD51B Gene-Disease associations (from GenCC):

• primary ovarian failure

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_133510.4	c.853+3508G>T		intron_variant	Intron 8 of 10	ENST00000471583.6	NP_598194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000471583.6	c.853+3508G>T		intron_variant	Intron 8 of 10	1	NM_133510.4	ENSP00000418859.1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79291 AN: 151882 Hom.: 22951 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.504

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.522 AC: 79349 AN: 152000 Hom.: 22972 Cov.: 32 AF XY: 0.524 AC XY: 38915 AN XY: 74296

African (AFR) AF: 0.253 AC: 10488 AN: 41464

American (AMR) AF: 0.647 AC: 9880 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1797 AN: 3472

East Asian (EAS) AF: 0.534 AC: 2760 AN: 5164

South Asian (SAS) AF: 0.651 AC: 3139 AN: 4822

European-Finnish (FIN) AF: 0.600 AC: 6328 AN: 10546

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.635 AC: 43175 AN: 67948

Other (OTH) AF: 0.503 AC: 1062 AN: 2112

Alfa AF: 0.604 Hom.: 67236

Bravo AF: 0.509

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.0
DANN	Benign	0.74
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11158728; hg19: chr14-68762205;